EP0429225A1 - Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen - Google Patents

Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen Download PDF

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Publication number
EP0429225A1
EP0429225A1 EP90312250A EP90312250A EP0429225A1 EP 0429225 A1 EP0429225 A1 EP 0429225A1 EP 90312250 A EP90312250 A EP 90312250A EP 90312250 A EP90312250 A EP 90312250A EP 0429225 A1 EP0429225 A1 EP 0429225A1
Authority
EP
European Patent Office
Prior art keywords
drug active
composition according
periodontal
compositions
composition
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP90312250A
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English (en)
French (fr)
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EP0429225B1 (de
Inventor
Nalinkant Chunilal Damani
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Procter and Gamble Co
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Procter and Gamble Co
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Filing date
Publication date
Application filed by Procter and Gamble Co filed Critical Procter and Gamble Co
Publication of EP0429225A1 publication Critical patent/EP0429225A1/de
Application granted granted Critical
Publication of EP0429225B1 publication Critical patent/EP0429225B1/de
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0063—Periodont
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis

Definitions

  • compositions/devices for treating diseases of the oral cavity, which compositions/devices are placed in or around the periodontal pocket.
  • the invention also relates to methods of using the compositions/devices in humans and lower animals suffering from such diseases.
  • Periodontal disease for example, is a major cause of tooth loss in adults. Tooth loss from periodontal disease is a significant problem beginning at age 35, but even by age 15 it is estimated that about 4 out of 5 persons already have gingivitis and 4 out of 10 have periodontitis.
  • the present inventor has discovered that using polypropenoic acid as the material forming the composition/device allows for efficient/good devices to be formed.
  • This invention utilizing highly swell able polymer eliminates such problems. Once a product of this invention is placed in periodontal cavity, the polymer swells, expands, and reaches narrow crevices and furcations of the treated cavity, carrying active agent throughout the cavity. This provides most desirable efficacy at treatment site.
  • the present invention relates to compositions/devices and methods for treating diseases of the oral cavity by inserting the compositions/devices around or into the periodontal pocket of humans and lower animals.
  • the compositions/devices comprise polypropenoic acid and an agent providing relief of diseases of the oral cavity such as periodontal disease.
  • compositions/devices of this invention are described below.
  • the polymer used in the present compositions is referred as super absorbent polymer and is defined as polypropenoic acid.
  • the material is a polyacrylic acid which is lightly crosslinked with an agent such as divinyl glycol, trimethylpropane triacrylate and polyallyl sucrose. These materials are provided as Dry Tech 512 by Dow Chemical Company, Aqualac-CA by Nippon Shokubai and NALCO-1181 by Nalco Chemicals. Other materials related to the above include Polycarbophil by B. F. Goodrich Company.
  • a preferred material is Dry Tech-512 which is polyacrylic acid crosslinked with 0.004 mole percent of trimethylpropane triacrylate.
  • the carboxylic groups can be neutralized with, for example, a sodium base to an extent of 75% or more.
  • a most preferred polymer useful in the present invention has very high, nearly infinite molecular weight in its crosslinked form which is estimated to be 2 million to 10 million or even higher.
  • Unit segments of crosslinked polymer have a range of number average molecular weight from about 50,000 to about 1 million.
  • the polymer is used in the present compositions at a level of from about 1% to about 99%, preferably from about 10% to about 75%, most preferably from about 20% to about 50%.
  • the drugs useful for use in the present compositions/devices are varied and many and include any agent which provides treatment of the disease.
  • Some therapeutic agents which are amenable to delivery by this means and are potentially of value for periodontal therapy include (but are not limited to) antimicrobial/antibacterial agents such as iodine, sulfonamides, mercurials, bisbiguanides, or phenolics; antibiotics such as tetracycline, neomycin, kanamycin, metronidazole, or clindamycin; antiinflammatory agents such as aspirin, naproxen, ibuprofen, flurbiprofen, indomethacin, eugenol, or hydrocortisone; immune-suppressive or stimulatory agents such as methotrexate or levamasole; dentinal desensitizing agents such as strontium chloride or sodium fluoride; odor masking agents such as peppermint oil or chlorphyll; immune reagents such as
  • the drug active is used at a level of from about 1% to about 99%, preferably from about 5% to about 75%, most preferably from about 10% to about 50% of the compositions/devices.
  • the compositions/devices are designed to release drug at a rate to provide concentration of from about 10 ⁇ g to about 2000 ⁇ g, preferably from about 50 ⁇ g to about 1000 ⁇ g, most preferably from about 100 ⁇ g to about 500 ⁇ g per milliliter of the gingival crevicular fluid of a treated periodontal pocket. Desired release rates can be achieved by altering ratios of components in a composition.
  • compositions/devices of the present invention may include a variety of optional components.
  • Such components include, but are not limited to, surfactants, other polymers, viscosity controlling agents, complexing agents, antioxidants, gums such as guar gum, waxes/oils such as castor wax, castor oil, glycerol, dibutyl phthalate and ethyl sebacate as well as many others.
  • the additional polymer may include a number of polymers such as methyl cellulose, polycaprolactone and polylactide.
  • a particularly preferred polymer is a copolymer of lactide and glycolide. Lactide monomeric species preferably comprise 15% to about 85%, most preferably from about 35% to about 65%, of the polymers while glycolide monomers comprise from about 15% to about 85% of the polymer, preferably from about 35% to about 65% on a molar basis.
  • the molecular weight lies in the range of from about 1000 to about 120,000 (number average).
  • these optional components comprise from about 0.1% to about 50%, preferably from about 0.5% to about 25% of the total composition/device.
  • compositions/devices of this invention are disclosed in the Examples.
  • composition/device of the present invention Weight % Tetracycline hydrochloride 50 Polypropenoic acid 22.7 Poly(lactyl-co-glycolide)/50:50 copolymer 22.7 Propylene Carbonate 4.6
  • the above composition can be prepared in a number of different ways.
  • One way is as follows: Polymer is charged into 110°C, electrically heated mixer, equipped with high shear Sigma type rotor blades. Propylene carbonate is added and mixed into the polymer. The drug is added and mixed until uniform. The drug polymer blend is removed for further processing into desired size and shaped devices.
  • compositions/devices of the invention of this application are inserted into or around the periodontal pocket or gingival region, and are administered in the form of a particle, film or sheet.
  • the size, shape, and thickness can be changed according to the condition of the periodontal disease to be treated and they are not particularly critical. Ordinarily, the size, shape, and thickness are changed according to the size of the periodontal pocket of the patient or the condition of the gingiva.
  • the devices may be for example of a size such that the thickness is in the range of 0.01 to 2mm, preferably from about 0.1 to about 1mm; the width in the range of 0.1 to about 5mm, preferably from about 0.2 to about 4mm; and the length in the range of from about 1 to about 15mm, preferably from about 3 to about 10mm.
  • Chlorhexidine acetate 40 Polypropenoic acid 35 Methyl Cellulose 20 Glycerol monostearate 5
  • composition/device representative of the present invention Wt. % Metronidazole 40 Polypropenoic acid 30 Polycaprolactone 25 Pluronic F-68 5
  • composition representative of the present invention Wt. % Flurbiprofen 20 Polypropenoic acid 25 Xanthan Gum 20 Polylactide polymer 25 Polyethylene glycol 10

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Physiology (AREA)
  • Nutrition Science (AREA)
  • Inorganic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Cosmetics (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
EP90312250A 1989-11-17 1990-11-08 Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen Expired - Lifetime EP0429225B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US07/438,545 US5084267A (en) 1989-11-17 1989-11-17 Sustained release compositions for treating periodontal disease
US438545 1989-11-17

Publications (2)

Publication Number Publication Date
EP0429225A1 true EP0429225A1 (de) 1991-05-29
EP0429225B1 EP0429225B1 (de) 1996-02-07

Family

ID=23741037

Family Applications (1)

Application Number Title Priority Date Filing Date
EP90312250A Expired - Lifetime EP0429225B1 (de) 1989-11-17 1990-11-08 Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen

Country Status (15)

Country Link
US (1) US5084267A (de)
EP (1) EP0429225B1 (de)
JP (1) JPH03209312A (de)
KR (1) KR0156918B1 (de)
AT (1) ATE133859T1 (de)
AU (1) AU648279B2 (de)
CA (1) CA2029047C (de)
DE (1) DE69025271T2 (de)
DK (1) DK0429225T3 (de)
ES (1) ES2082834T3 (de)
FI (1) FI98125C (de)
GR (1) GR3018934T3 (de)
IE (1) IE71930B1 (de)
NZ (1) NZ236112A (de)
PT (1) PT95868B (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995009601A1 (en) * 1993-10-01 1995-04-13 The Procter & Gamble Company Use of azithromycin for the treatment of adult periodontitis and topical compositions for this use
EP0671175A2 (de) * 1989-11-17 1995-09-13 The Procter & Gamble Company Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen
US7108865B2 (en) 1994-05-06 2006-09-19 Pfizer Inc Controlled-release dosage forms of azithromycin

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5770588A (en) * 1991-02-11 1998-06-23 The Research Foundation Of State University Of New York Non-antibacterial tetracycline compositions of the prevention and treatment of root caries
US5330768A (en) * 1991-07-05 1994-07-19 Massachusetts Institute Of Technology Controlled drug delivery using polymer/pluronic blends
US5922340A (en) * 1992-09-10 1999-07-13 Children's Medical Center Corporation High load formulations and methods for providing prolonged local anesthesia
US5242910A (en) * 1992-10-13 1993-09-07 The Procter & Gamble Company Sustained release compositions for treating periodontal disease
US5447725A (en) * 1993-06-11 1995-09-05 The Procter & Gamble Company Methods for aiding periodontal tissue regeneration
DE69632569T2 (de) * 1995-06-09 2005-08-18 Euroceltique S.A. Formulierungen und verfahren für eine verlängerte lokalanästhesie
US5814331A (en) * 1995-11-13 1998-09-29 Holen; Sheldon Process for inhibiting pathogenic bacteria in the oral cavity and for binding peptide growth factors on surfaces
AU733867B2 (en) 1996-06-24 2001-05-31 Euro-Celtique S.A. Methods for providing safe local anesthesia
US6046187A (en) * 1996-09-16 2000-04-04 Children's Medical Center Corporation Formulations and methods for providing prolonged local anesthesia
KR100367144B1 (ko) 1997-07-02 2003-01-14 유로-셀티크 소시에떼 아노뉨 관절과 체강(ｂｏｄｙ ｓｐａｃｅ)내에서 연장된 마취
WO1999012640A1 (en) 1997-09-09 1999-03-18 Select Release, L.C. Coated particles, methods of making and using
US6638621B2 (en) * 2000-08-16 2003-10-28 Lyotropic Therapeutics, Inc. Coated particles, methods of making and using
EP1071400B1 (de) * 1998-04-20 2004-11-03 Genzyme Corporation Medikamentöse verabreichung von proteinen aus polymergemischen
WO2002058670A1 (en) * 2001-01-25 2002-08-01 Euroceltique S.A. Local anesthetic, and method of use
US20060147394A1 (en) * 2004-12-30 2006-07-06 Ramachandra Shastry Tooth whitening composition containing cross-linked polymer-peroxides
US7125954B2 (en) * 2005-01-27 2006-10-24 General Electric Company Method for producing polyether polymers
US20120065221A1 (en) 2009-02-26 2012-03-15 Theraquest Biosciences, Inc. Extended Release Oral Pharmaceutical Compositions of 3-Hydroxy-N-Methylmorphinan and Method of Use

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US4250163A (en) * 1979-03-05 1981-02-10 Teijin Limited Method and preparation for administration to the mucosa of the oral or nasal cavity
EP0130690A2 (de) * 1983-06-01 1985-01-09 Teijin Limited Pharmazeutische Zubereitung zur Heilung der Erkrankungen der Zahnwurzelhaut und Verfahren zu deren Herstellung
WO1985002092A1 (en) * 1983-11-14 1985-05-23 Bio-Mimetics Inc. Bioadhesive compositions and methods of treatment therewith
US4568536A (en) * 1985-02-08 1986-02-04 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
EP0241178A1 (de) * 1986-03-25 1987-10-14 Rohto Pharmaceutical Co., Ltd. Arzneimittel zur Behandlung periodontaler Erkrankungen
EP0267617A1 (de) * 1986-11-14 1988-05-18 Theratech, Inc. Erhöhung des Penetrationsvermögens mittels eines aus die Zellhülle verändernden Substanzen und kurzkettigen Alkoholen bestehenden binären Systems
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EP0130690A2 (de) * 1983-06-01 1985-01-09 Teijin Limited Pharmazeutische Zubereitung zur Heilung der Erkrankungen der Zahnwurzelhaut und Verfahren zu deren Herstellung
WO1985002092A1 (en) * 1983-11-14 1985-05-23 Bio-Mimetics Inc. Bioadhesive compositions and methods of treatment therewith
US4568536A (en) * 1985-02-08 1986-02-04 Ethicon, Inc. Controlled release of pharmacologically active agents from an absorbable biologically compatible putty-like composition
EP0241178A1 (de) * 1986-03-25 1987-10-14 Rohto Pharmaceutical Co., Ltd. Arzneimittel zur Behandlung periodontaler Erkrankungen
EP0267617A1 (de) * 1986-11-14 1988-05-18 Theratech, Inc. Erhöhung des Penetrationsvermögens mittels eines aus die Zellhülle verändernden Substanzen und kurzkettigen Alkoholen bestehenden binären Systems
EP0275550A1 (de) * 1986-12-24 1988-07-27 Teikoku Seiyaku Kabushiki Kaisha Klebeinrichtung zur Anwendung an Körpergewebe

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0671175A2 (de) * 1989-11-17 1995-09-13 The Procter & Gamble Company Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen
EP0671175A3 (de) * 1989-11-17 1996-02-28 Procter & Gamble Pharmazeutische Zubereitungen mit verzögerter Freisetzung zur Behandlung periodontaler Erkrankungen.
WO1995009601A1 (en) * 1993-10-01 1995-04-13 The Procter & Gamble Company Use of azithromycin for the treatment of adult periodontitis and topical compositions for this use
US7108865B2 (en) 1994-05-06 2006-09-19 Pfizer Inc Controlled-release dosage forms of azithromycin

Also Published As

Publication number Publication date
IE71930B1 (en) 1997-03-12
CA2029047A1 (en) 1991-05-18
KR0156918B1 (ko) 1998-11-16
FI98125B (fi) 1997-01-15
FI905681A (fi) 1991-05-18
FI98125C (fi) 1997-04-25
DK0429225T3 (da) 1996-06-24
US5084267A (en) 1992-01-28
IE904148A1 (en) 1991-05-22
KR910009241A (ko) 1991-06-28
AU648279B2 (en) 1994-04-21
CA2029047C (en) 1995-03-14
JPH03209312A (ja) 1991-09-12
DE69025271D1 (de) 1996-03-21
DE69025271T2 (de) 1996-09-05
AU6667790A (en) 1991-05-23
PT95868A (pt) 1991-09-30
GR3018934T3 (en) 1996-05-31
EP0429225B1 (de) 1996-02-07
NZ236112A (en) 1993-04-28
ES2082834T3 (es) 1996-04-01
FI905681A0 (fi) 1990-11-16
PT95868B (pt) 1997-11-28
ATE133859T1 (de) 1996-02-15

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